Radical Local Therapy Offers Mortality Benefit in Very High-Risk PCa

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Prostatectomy and radiotherapy with or without ADT reduced prostate cancer-specific and all-cause mortality rates.

Guidelines recommend androgen deprivation therapy (ADT) only for men with very high-risk prostate cancer (PCa), but new findings from a population-based study suggest that radical local treatment can lower mortality in these patients.

The study, by Pär Stattin, MD, of Uppsala University in Uppsala, Sweden, and colleagues, included 7500 men with very high-risk PCa (local clinical stage T4 and/or PSA level 50–200 ng/mL, any nodal involvement, and no known metastases) and 10,316 men with locally advanced PCa (local clinical stage T3 and PSA level less than 50 ng/mL, any nodal involvement, and no known metastases) who served as positive controls.

Dr Stattin’s group examined the proportion of men who received primary radical local therapy—radical prostatectomy or full-dose radiotherapy with or without androgen deprivation therapy—within 1 year of diagnosis for very high-risk and locally advanced PCa in 640 experimental units defined by county, diagnostic period, and age at diagnosis.

PCa-specific and all-cause mortality rates were 49% and 44% lower in units in the highest tertile of exposure to radical local treatment (67%–100%) compared with units in the lowest tertile (0%–33%), Dr Stattin and colleagues reported online ahead of print in European Urology.

The PCa-specific and all-cause mortality rates observed for locally advanced PCa were 25% and 15% lower in units in the highest versus lowest tertile of exposure.

In the very high-risk PCa group, the association between radical treatment and PCa mortality for highest versus lowest tertile of exposure was observed in all age groups up to 75 years, the investigators reported. Among men younger than 65 years and those aged 65–69 years and 70–74 years, those in the highest tertile of exposure had PCa-specific mortality rates 36%, 68%, and 12% lower than those in the lowest tertile, respectively.

The absolute PCa-specific mortality for men with very high-risk PCa was 30 per 1000 person-years in the highest tertile compared with 58 per 1000 person-years in the lowest tertile. The absolute all-cause mortality for these men was 44 and 79 per 1000 person-years, respectively.

The investigators concluded that their study findings suggest “that radical local treatment decreases mortality in men with very high-risk PCa for whom radical treatment has previously been considered ineffective.”

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With respect to study strengths, Dr Stattin’s group noted that exposure to treatment could be assessed on a population level, which minimized selection bias on an individual level, while at the same time they had available comprehensive, high-quality individual-level data for cancer characteristics, comorbidity, cancer treatment, and cause of death.

The investigators acknowledged that the effects of diagnostic and therapeutic activity could not be separated. “High exposure to radical local treatment was linked to high exposure to staging investigations including bone and lymph node imaging and complete Gleason classification,” they wrote.